World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 000, Number 000, July 2026, pages 000-000

Prediction of Residual Disease in Unresectable Head and Neck Squamous Cell Carcinoma After Concurrent Chemoradiotherapy

↓ Figure 1. Study flow diagram. CCRT: concurrent chemoradiotherapy; CT: computed tomography; MRI: magnetic resonance imaging.

↓ Figure 3. Calibration plot demonstrating the agreement between the predicted and observed probabilities of residual disease (RD). AUC shown in the plot is equivalent to AuROC. O:E ratio: observed-to-expected ratio; CITL: calibration-in-the-large.

↓ Figure 4. Decision curve analysis demonstrating the net clinical benefit of the prediction model for residual disease.

↓ Figure 5. The predicted probability of residual disease (RD) plotted against the model’s linear predictor (xb), highlighting the threshold used for clinical decision-making. The linear predictor cutoff (xb cut) of −0.1161 corresponds to a predicted probability of 0.471.

↓ **Table 1.** Baseline Characteristics Associated With Treatment Response (Residual Disease vs. Complete Response)
Prognostic factors	Residual disease (n = 180), n (%)	Complete response (n = 202), n (%)	P value	AuROC
HPV testing was performed mainly in patients with oropharyngeal tumors. Histological grade was missing in one patient with residual disease. AuROC: area under the receiver operating characteristic curve; BMI: body mass index; HPV: human papillomavirus; IQR: interquartile range; NLR: neutrophil-to-lymphocyte ratio; SD: standard deviation.
Male sex	75 (41.7)	91 (45.0)	0.536	0.516
Age (years), mean ± SD	55.9 ± 9.9	58.4 ± 11.0	0.018	0.585
Comorbidities
Diabetes mellitus	8 (4.4)	11 (5.4)	0.814	0.505
Hypertension	23 (12.8)	36 (17.8)	0.202	0.525
Dyslipidemia	9 (5.0)	19 (9.4)	0.117	0.522
Smoking history	119 (66.1)	121 (59.9)	0.243	0.531
Alcohol consumption	111 (61.7)	122 (60.4)	0.834	0.506
Tumor site			< 0.001	0.683
Supraglottis	12 (6.7)	50 (24.8)
Oropharynx	72 (40.0)	105 (52.0)
Hypopharynx	70 (38.9)	35 (17.3)
Oral cavity	26 (14.4)	12 (5.9)
Histologic grade			0.698	0.522
Well differentiated	55 (30.8)	70 (34.7)
Moderately differentiated	91 (50.8)	95 (47.0)
Poorly differentiated	33 (18.4)	37 (18.3)
Tumor stage (T-stage)			< 0.001	0.723
T1	8 (4.4)	17 (8.4)
T2	18 (10.0)	53 (26.2)
T3	35 (19.4)	86 (42.6)
T4	119 (66.1)	46 (22.8)
Nodal stage (N-stage)			< 0.001	0.689
N1	30 (16.7)	91 (45.0)
N2	112 (62.2)	106 (52.5)
N3	38 (21.1)	5 (2.5)
Hemoglobin (g/dL), mean ± SD	11.2 ± 1.9	12.2 ± 1.9	< 0.001	0.641
Albumin (g/dL), mean ± SD	3.7 ± 0.5	3.9 ± 0.4	0.001	0.617
HPV-positive	6 (7.6)	53 (41.4)	0.001	0.669
NLR, median (IQR)	4.3 (2.7, 7.1)	3.0 (1.9, 4.4)	< 0.001	0.670
Maximum tumor diameter (cm), median (IQR)	6.5 (5.7, 7.3)	3.5 (2.5, 4.7)	< 0.001	0.914
Tumor size anteroposterior (cm), mean ± SD	4.4 ± 1.8	2.8 ± 1.3	< 0.001	0.761
Tumor size transverse (cm), mean ± SD	4.5 ± 1.7	2.7 ± 1.2	< 0.001	0.793
Tumor size vertical (cm), mean ± SD	5.7 ± 2.0	3.1 ± 1.5	< 0.001	0.850
Maximum lymph node diameter (cm), median (IQR)	2.0 (1.2, 5.0)	1.8 (1.0, 3.0)	0.169	0.563
BMI (kg/m²), mean ± SD	18.9 ± 3.1	20.4 ± 3.9	< 0.001	0.615
Time to initiation of radiotherapy (days), median (IQR)	62.0 (49.5, 84.5)	61.0 (52.0, 75.0)	0.217	0.538
Overall treatment time (days), mean ± SD	54.5 ± 10.8	52.5 ± 18.9	0.470	0.566

↓ Table 1. Baseline Characteristics Associated With Treatment Response (Residual Disease vs. Complete Response)

Prognostic factors

Residual disease (n = 180), n (%)

Complete response (n = 202), n (%)

P value

AuROC

HPV testing was performed mainly in patients with oropharyngeal tumors. Histological grade was missing in one patient with residual disease. AuROC: area under the receiver operating characteristic curve; BMI: body mass index; HPV: human papillomavirus; IQR: interquartile range; NLR: neutrophil-to-lymphocyte ratio; SD: standard deviation.

Male sex

75 (41.7)

91 (45.0)

0.536

0.516

Age (years), mean ± SD

55.9 ± 9.9

58.4 ± 11.0

0.018

0.585

Comorbidities

Diabetes mellitus

8 (4.4)

11 (5.4)

0.814

0.505

Hypertension

23 (12.8)

36 (17.8)

0.202

0.525

Dyslipidemia

9 (5.0)

19 (9.4)

0.117

0.522

Smoking history

119 (66.1)

121 (59.9)

0.243

0.531

Alcohol consumption

111 (61.7)

122 (60.4)

0.834

0.506

Tumor site

< 0.001

0.683

Supraglottis

12 (6.7)

50 (24.8)

Oropharynx

72 (40.0)

105 (52.0)

Hypopharynx

70 (38.9)

35 (17.3)

Oral cavity

26 (14.4)

12 (5.9)

Histologic grade

0.698

0.522

Well differentiated

55 (30.8)

70 (34.7)

Moderately differentiated

91 (50.8)

95 (47.0)

Poorly differentiated

33 (18.4)

37 (18.3)

Tumor stage (T-stage)

< 0.001

0.723

8 (4.4)

17 (8.4)

18 (10.0)

53 (26.2)

35 (19.4)

86 (42.6)

119 (66.1)

46 (22.8)

Nodal stage (N-stage)

< 0.001

0.689

30 (16.7)

91 (45.0)

112 (62.2)

106 (52.5)

38 (21.1)

5 (2.5)

Hemoglobin (g/dL), mean ± SD

11.2 ± 1.9

12.2 ± 1.9

< 0.001

0.641

Albumin (g/dL), mean ± SD

3.7 ± 0.5

3.9 ± 0.4

0.001

0.617

HPV-positive

6 (7.6)

53 (41.4)

0.001

0.669

NLR, median (IQR)

4.3 (2.7, 7.1)

3.0 (1.9, 4.4)

< 0.001

0.670

Maximum tumor diameter (cm), median (IQR)

6.5 (5.7, 7.3)

3.5 (2.5, 4.7)

< 0.001

0.914

Tumor size anteroposterior (cm), mean ± SD

4.4 ± 1.8

2.8 ± 1.3

< 0.001

0.761

Tumor size transverse (cm), mean ± SD

4.5 ± 1.7

2.7 ± 1.2

< 0.001

0.793

Tumor size vertical (cm), mean ± SD

5.7 ± 2.0

3.1 ± 1.5

< 0.001

0.850

Maximum lymph node diameter (cm), median (IQR)

2.0 (1.2, 5.0)

1.8 (1.0, 3.0)

0.169

0.563

BMI (kg/m²), mean ± SD

18.9 ± 3.1

20.4 ± 3.9

< 0.001

0.615

Time to initiation of radiotherapy (days), median (IQR)

62.0 (49.5, 84.5)

61.0 (52.0, 75.0)

0.217

0.538

Overall treatment time (days), mean ± SD

54.5 ± 10.8

52.5 ± 18.9

0.470

0.566

↓ **Table 2.** Model Development and Predictors of Residual Disease
Predictors	Univariable OR (95% CI)	P value	Multivariable OR (95% CI)	P value
Overall multivariable model AuROC was 0.929. BMI: body mass index; CI: confidence interval; NLR: neutrophil-to-lymphocyte ratio; OR: odds ratio.
Tumor site
Supraglottis	1.00 (Reference)	-	1.00 (Reference)	-
Oropharynx	2.85 (1.42, 5.74)	0.003	1.39 (0.46, 4.20)	0.551
Hypopharynx	8.33 (3.93, 17.63)	< 0.001	3.56 (1.10, 11.40)	0.033
Oral cavity	9.02 (3.56, 22.88)	< 0.001	3.77 (0.95, 14.90)	0.058
Maximum tumor diameter (cm)	3.47 (2.72, 4.43)	< 0.001	3.37 (2.59, 4.39)	< 0.001
Hemoglobin (g/dL)	0.76 (0.68, 0.85)	< 0.001	0.94 (0.79, 1.11)	0.475
NLR	1.15 (1.07, 1.22)	< 0.001	1.02 (0.94, 1.10)	0.610
BMI (kg/m²)	0.88 (0.83, 0.94)	< 0.001	0.97 (0.88, 1.06)	0.519
Time to initiation of radiotherapy (days)	1.01 (1.00, 1.02)	0.005	1.01 (1.00, 1.02)	0.016

↓ Table 2. Model Development and Predictors of Residual Disease

Predictors

Univariable OR (95% CI)

P value

Multivariable OR (95% CI)

P value

Overall multivariable model AuROC was 0.929. BMI: body mass index; CI: confidence interval; NLR: neutrophil-to-lymphocyte ratio; OR: odds ratio.

Tumor site

Supraglottis

1.00 (Reference)

Oropharynx

2.85 (1.42, 5.74)

0.003

1.39 (0.46, 4.20)

0.551

Hypopharynx

8.33 (3.93, 17.63)

< 0.001

3.56 (1.10, 11.40)

0.033

Oral cavity

9.02 (3.56, 22.88)

< 0.001

3.77 (0.95, 14.90)

0.058

Maximum tumor diameter (cm)

3.47 (2.72, 4.43)

< 0.001

3.37 (2.59, 4.39)

< 0.001

Hemoglobin (g/dL)

0.76 (0.68, 0.85)

< 0.001

0.94 (0.79, 1.11)

0.475

NLR

1.15 (1.07, 1.22)

< 0.001

1.02 (0.94, 1.10)

0.610

BMI (kg/m²)

0.88 (0.83, 0.94)

< 0.001

0.97 (0.88, 1.06)

0.519

Time to initiation of radiotherapy (days)

1.01 (1.00, 1.02)

0.005

1.01 (1.00, 1.02)

0.016

↓ **Table 3.** Model Performance and Internal Validation
Parameters	Apparent performance (95% CI)	Bootstrap-corrected performance (95% CI)
AuROC: area under the receiver operating characteristic curve; CI: confidence interval; CITL: calibration-in-the-large; O:E ratio: observed-to-expected outcomes ratio.
C-statistic (AuROC)	0.929 (0.903, 0.954)	0.929 (0.905, 0.956)
O:E ratio	1.000	1.002 (0.930, 1.070)
CITL	0.000 (−0.304, 0.304)	−0.004 (−0.324, 0.323)
Calibration slope	1.000 (0.801, 1.199)	0.997 (0.776, 1.232)
Bootstrap shrinkage	-	0.997

↓ Table 3. Model Performance and Internal Validation

Parameters

Apparent performance (95% CI)

Bootstrap-corrected performance (95% CI)

AuROC: area under the receiver operating characteristic curve; CI: confidence interval; CITL: calibration-in-the-large; O:E ratio: observed-to-expected outcomes ratio.

C-statistic (AuROC)

0.929 (0.903, 0.954)

0.929 (0.905, 0.956)

O:E ratio

1.000

1.002 (0.930, 1.070)

CITL

0.000 (−0.304, 0.304)

−0.004 (−0.324, 0.323)

Calibration slope

1.000 (0.801, 1.199)

0.997 (0.776, 1.232)

Bootstrap shrinkage

0.997

↓ **Table 4.** Classification Performance at a Predicted Probability Threshold of 0.471
Model probability of residual disease	Residual disease (n = 180), n (% of total cohort)	Complete response (n = 202), n (% of total cohort)	PPV (%) (95% CI)	NPV (%) (95% CI)
Percentages are cell percentages calculated using the total study population (N = 382) as the denominator. CI: confidence interval; NPV: negative predictive value; PPV: positive predictive value.
≥ 0.471	160 (41.9)	37 (9.7)	81.2 (75.1, 86.4)	89.2 (83.8, 93.3)
< 0.471	20 (5.2)	165 (43.2)

↓ Table 4. Classification Performance at a Predicted Probability Threshold of 0.471

Model probability of residual disease

Residual disease (n = 180), n (% of total cohort)

Complete response (n = 202), n (% of total cohort)

PPV (%) (95% CI)

NPV (%) (95% CI)

Percentages are cell percentages calculated using the total study population (N = 382) as the denominator. CI: confidence interval; NPV: negative predictive value; PPV: positive predictive value.

≥ 0.471

160 (41.9)

37 (9.7)

81.2 (75.1, 86.4)

89.2 (83.8, 93.3)

< 0.471

20 (5.2)

165 (43.2)